CN103930133A - In-situ cross-linkable polymeric compositions and methods thereof - Google Patents
In-situ cross-linkable polymeric compositions and methods thereof Download PDFInfo
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- CN103930133A CN103930133A CN201280055699.0A CN201280055699A CN103930133A CN 103930133 A CN103930133 A CN 103930133A CN 201280055699 A CN201280055699 A CN 201280055699A CN 103930133 A CN103930133 A CN 103930133A
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- 229920000669 heparin Polymers 0.000 description 1
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- 238000006703 hydration reaction Methods 0.000 description 1
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- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
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- TWNIBLMWSKIRAT-VFUOTHLCSA-N levoglucosan Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@H]2CO[C@@H]1O2 TWNIBLMWSKIRAT-VFUOTHLCSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
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- 230000000813 microbial effect Effects 0.000 description 1
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- 210000000056 organ Anatomy 0.000 description 1
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- 230000002093 peripheral effect Effects 0.000 description 1
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Classifications
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
- A61L26/0052—Mixtures of macromolecular compounds
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
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- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
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- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
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- A—HUMAN NECESSITIES
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- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
- A61L26/0014—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
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- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
- A61L26/0023—Polysaccharides
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- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0061—Use of materials characterised by their function or physical properties
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- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
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- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
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- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F283/00—Macromolecular compounds obtained by polymerising monomers on to polymers provided for in subclass C08G
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- A61L2400/00—Materials characterised by their function or physical properties
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Abstract
A biocompatible polymeric composition for cross-linking in-situ in a wound is disclosed comprising 1) one or more polyanionic polymers such as alginates or hyaluronates, able to be cross-linked the surface of the wound and 2) one or more polycationic polymers such as chitosan or DEAE-Dextran, that assists in the solidification process as well as speeds up hemostasis without the need for applying pressure. The biocompatible polymeric composition may further comprise a cross-linking agent such as aqueous calcium chloride. The invention encompasses an initial polymeric composition, the solidified matrix cross-linked and integrated at the wound site, including the methods of using, applying, and cross-linking the composition.
Description
The application requires the temporary patent application the 61/559th of submitting on November 13rd, 2011, the rights and interests of No. 110, and it is incorporated to herein by reference of text.
Technical field
The present invention relates generally to use the compositions of bioavailable polymer goods, and relate to particularly close blood (hemophilic) polymeric matrix using in wound healing, blood coagulation and cosmetic use.
Background technology
Wound healing is complicated, and the accurate process of coordinating, relates to the interaction of various cells and matrix components, tentatively to set up interim tissue and to be reinvented afterwards, forms ripe substitute simultaneously.At first, the platelet bolt of hemostasis re-establishes the barrier that restriction is infected and restriction is dewatered, and causes first wave cellular infiltration.This is mainly by congenital and Leucocyles acquired immunity is provided.These cells generation enzymes and biocidal molecule are to eliminate microbial contamination; Yet organize required keratinocyte, fibroblast and endotheliocyte that these identical defense mechanisms lose for regeneration are disadvantageous.Therefore,, along with treatment is carried out, event and the process need of inflammatory stage disappear.
The situation of carrying out skin wound reparation on contaminated surface has proposed special challenge.If wound is infected, chronic when becoming along with inflammatory stage, heal normally destroyed, suppress the regeneration stage.Further, the enzyme that microorganism and leukocyte discharge damages wound tissue and skin around.Therefore, key is to guarantee suitable healing, with the infection that prevents that normal skin wound contamination from setting up.
Wound healing is divided into three phases conventionally: inflammatory stage, multiplicative stage and reinventing the stage.Fibronectin has been in the news and has participated in each stage in wound healing process, and the cell of particularly invading by generation is by the skeleton adhering to.At first, many media are discharged into wound location, for example fibronectin and Fibrinogen.Fibronectin promotes that inflammatory cell moves to wound and monocytic fragment phagocytosis.After this, angiogenesis and re-epithelialization occur.In this stage, fibronectin vascular endothelial cell is applied to chemotactic activity and promote epithelial cell and migration of fibroblast cells to basement membrane.It is also necessary that fibronectin seemed in the stage of reinventing, and wherein it plays a major role in the group structure of collagen fiber.Fibrous collagen protein finally forms the fibre bundle of the tensile strength that strengthens tissue, makes wound closure.
Hydrogel is often used as the local goods that promote wound healing process.Due to the characteristic of swelling degree, biocompatibility, permeability and the Swelling Dynamics of gel combination, and selected gel combination.The example of this compounds comprises polyvinyl (for example polyacrylic acid), cellulose and cellulose derivative.Acrylic acid polymer, is also referred to as carbomer, because it is providing the superiority on fibronectin to be used to skin wound.
Naturally occurring biopolymer obtains application in organizational project, regenerative medicine, drug delivery, medical implant, plastic surgery and other field.This series products has the component that comprises hyaluronic acid (HA), chitosan, heparin, chondroitin sulfate, alginate and other glycosamine and glucosaminoglycan, other polysaccharide and derivant thereof.
With combining form, the concentration of fibronectin (and similar protein) has been used for the treatment of chronic ulcer together with alginate.Dressing system solidifies by freeze-drying process, and gel is changed into fiber.This process produces the spongy architecture with water-wet behavior.When fluid exists, dressing can be turned back to gel sample state, absorb up to 20 times to the Wound exudate of own wt.Dressing is easily removed because of its spongy architecture and moisture retention after Wound healing and bone regeneration.Yet, once with saline solution hydration, the dressing of fibronectin-cellulose can not go on the human body skin surface of epithelization, to provide required fiber protecting film.Then, when removing dressing, carry out debridement to remove any downright bad material.
Therefore, in the treatment of acute and chronic wounds, have problems, comprise that the granulation of delayed union, minimizing forms and epithelization, and persistency wound inflammation.Impaired wound healing may cause other complication and problem, the development of for example infection, pain and chronic (non-healing) wound.
In the treatment of chronic wounds, there is at present and assist healing, minimizing inflammation, ease the pain and prevent from following the synulotic demand of acute and chronic wounds.This acute wounds being treated comprises burn, scratch, xerosis cutis, postoperative operative incision, hurts, stabs, blister, mosquito bite and other serious tissue injurys.Chronic wound treatment may contain the wound of slow healing, comprises decubital ulcer, venous ulcer, diabetic foot ulcer, decubitus ulcer and disunion tissue injury.
Generally, expectation is the compositions of application easily, and it is formed with and is beneficial to the substrate of organization healing and has antimicrobial property.Said composition can be biocompatible or fast reaction to avoid Cytotoxic probability.Further, described compositions can stimulate and maximized wound healing, simultaneously as required, is provided for providing the controlled method of the curing wound dressing of thin layer and thick-layer.
Remote-effects may comprise the needs that reduce medical procedure, for example debridement,, reduce the hospital stays, reduce the post-operative recovery time, shorten the cycle of recovering daily life function and operation, and reduce overall medical expense.It is desirable to, these improvement to wound healing, comprise application and using method, in treating and repairing various tissues, will be valuable.
Summary of the invention
Below invention is biocompatible polymer composition, and it is can be in inside and outside formation curing gel wound healing and hemostasis substrate.
In one embodiment of the invention, biocompatible polymer composition comprises: 1) one or more polyanion polymer and 2) one or more polycation polymer.In one embodiment of the invention, described one or more polyanion polymer comprises at least one crosslinkable polyanion polymer.In another embodiment of the invention, described one or more polyanion polymer comprises at least one crosslinkable polyanion polymer and at least one not crosslinkable polyanion polymer.
In one embodiment of the invention, described biocompatible polymer composition comprises 1) one or more the polyanion polymer and 2 that can form in wound surface) one or more the mixture of polycation polymer of assisting solidification process and accelerating blood coagulation.In another embodiment of the invention, biocompatible polymer composition comprises 1) one or more the polyanion polymer that can form in wound surface; 2) one or more the polycation polymer of assisting solidification process and accelerating blood coagulation; With 3) gel is cross-linked in wound simultaneously by the mixture of the crosslinked mist agent (mist) of peripheral region sterilization.
In one embodiment of the invention, described one or more polyanion polymer comprises alginate or hyaluronate.In one embodiment of the invention, described one or more polycation polymer comprises chitosan.In one embodiment of the invention, described crosslinked mist agent can be watersoluble chlorinated calcium.
Also disclose one or more methods of using medical gel of the present invention, comprised rapid realization hemostasis and without exerting pressure, and biocompatible wound healing substrate is provided.
Various embodiments of the present invention allow described goods adjust and use, to change desired viscosity and predetermined sign function.In one aspect, the ratio of polycation polymer and polyanion polymer may improve, and has effectiveness in various degree on wound healing.In yet another aspect, can add therapeutic agent to select object to integrate pharmaceutical preparation for drug delivery.In addition, further feature may contain in the preparation process of controlling described medical gel, the temperature in the process of application gel and/or pressure and carry out the control to the elasticity of solidification matrix or rigidity.Described substrate goods, two kinds of liquid and consolidated structures, also can depend on and dissect and physiological measurement result and condition.
Various embodiments of the present invention allow in the first tissue site or the second tissue site adjustment and use described compositions, and such modification can be regarded as significantly, and can integrate and combine so that the substrate of any size, shape and structure to be provided with different quantity.
Accompanying drawing explanation
Fig. 1 is the side view of embodiment of the present invention.
Fig. 2 is how the present invention describes with blood and the microcosmic himself reacting.
Fig. 3 A to Fig. 3 I shows the various polymer subunits that can be used to manufacture polyanion or polycation polymer.
Benefit of the present invention when Fig. 4 shows compared with prior art.
Detailed Description Of The Invention
Below describing in detail and gather, in order to illustrate rather than restricted object, show that the exemplary of open detail is to provide thorough understanding of the present invention.Yet, concerning persons skilled in the art, be apparent that the present invention can carry out in other embodiments that depart from detail disclosed herein.Other in the situation that, to knowing the detailed description of compositions and method, can omit in order to avoid obscure description of the invention.
Biocompatible polymer composition of the present invention can be used for treating external wounds and internal wounds.In one embodiment of the invention, biocompatible polymer composition can be applied to various wounds.The limiting examples of wound includes but not limited to: outside lacerated wound, wearing and tearing, burn, eye lacerated wound, organa parenchymatosum's damage, inner lacerated wound, gastrointestinal tract lacerated wound, shallow table incised wound and scratch, internal hemorrhage, arterial hemorrhage, venous hemorrhage, tooth or oral hemorrhage and otch.The experimenter that can benefit from these Wound healing and bone regenerations comprises various animals, comprises people, and mammal is horse, sheep, cattle, pig, Canis familiaris L., cat and marine animal whale, dolphin, sea dog, Lutra lutra, Fish and reptile Chelomia mydas (Linnaeus). for example for example for example.
Fig. 1 illustrates the structural matrix exemplary illustration according to one embodiment of the invention.As described, the impaired part of tissue, wound (112), has the vascular (116) that runs through outstanding.Biocompatible polymer compositions (114) has been applied to wound (112), and it has been coated with protective coating (110).
Fig. 2 shows the enlarged drawing of an embodiment of biocompatible polymer composition (114), and it comprises structural polymer (226) and close blood polymer (224).The crosslinkable polyanion polymer that structural polymer (226) comprises composition total weight meter approximately 0.1% to 95% and composition total weight meter 0% to 95% can not crosslinked poly anionic polymer.The polycation polymer that parent's blood polymer (224) comprises composition total weight meter approximately 1% to 90%.Erythrocyte (210) demonstration is associated with cationic functional groups (212) by erythrocyte-cation group bonding (216).
Fig. 3 A to 3I shows the various polymer that can be selected as structural polymer (226) or close blood polymer (224).Polymer can revise to obtain anionic functional group (218) by adding carboxymethyl (CM) group.Fig. 3 E shows carboxymethyl cellulose.Alginate (3A), hyaluronate sodium (3F), kappa carrageenan (3G), ι-carrageenan (3H) and sodium polyacrylate (3I) are the examples that plays the polymer of structural polymer (226) effect.Equally, chitin (3B) and chitosan (3C) are the examples of the polymer that works as close blood polymer (224).Fig. 3 D show arbitrary polymer (340) all available diethyllaminoethyl (DEAE) group revise to obtain Cationic functional groups (212).
The solvent that biocompatible polymer composition (114) contains composition total weight meter approximately 0.1% to 99.8%.In one embodiment of the invention, solvent is ethanol.Preferably, described solvent is 5% aqueous solution of ethanol in water.The limiting examples of solvent comprises water, ethanol, pentyl acetate, acetone, methyl ethyl ketone, isopropyl alcohol and oxolane.In solution, the intermolecular interaction that structural polymer (226) and close blood polymer (224) experience bond them together.Anionic functional group (218) on cationic functional groups (212) Attraction structure polymer (226) on parent's blood polymer (224), and produce ionomer (214).In addition, close blood polymer (224) and structural polymer (226) can be (228) of covalent cross-linking, are similar to Schiff's base or azomethine bonding.
The bivalence that protective finish (110) comprises weighing scale 0.1% to 30% or the more cation (220) of high price, the hydrophobic polymer of weighing scale 0% to 90%, and the solvent of weighing scale 5% to 99.9%.Protective finish (110) is by bivalent cation (220) cross-linked composition (114) to internal diffusion, and this produces the bivalent cation crosslinked (222) of structural polymer (226).This increases the rigidity of compositions (114) and allows better stability.Protective finish (110) can also comprise hydrophobic polymer, and its restriction, from the water loss of compositions (114), improves durability.Described hydrophobic polymer can be polyurethanes, nitrocellulose, cyanoacrylate, styrene, politef and silicone and combination thereof.Solvent can be water, pentyl acetate, acetone, methyl ethyl ketone, isopropyl alcohol and oxolane, and combination.This bivalence or more high-valence cationic can be Ca
2+, Fe
2+, Fe
3+, Ag
2+, Ag
3+, Au
2+, Au
3+, Mg
2+, Cu
2+, Cu
3+and Zn
2+.In an embodiment of the invention, described cation is Ca
2+.
In one embodiment of the invention, the hyaluronate sodium of the sodium alginate that structural polymer (226) comprises weighing scale 0.1% to 5% and weighing scale 1% to 5%, the chitosan acyl chlorides that parent's blood polymer (224) comprises weighing scale 2% to 25%, and 5% aqueous solution of the ethanol that solvent comprises weighing scale 65% to 96.9% in water.In this embodiment, described compositions plays wound healing substrate and does in order to promote tissue regeneration faster.
In another embodiment, the hyaluronate sodium of the sodium alginate that structural polymer (226) comprises weighing scale 2% to 5% and weighing scale 0% to 2%, the Sea Cure CL 313 that parent's blood polymer (224) comprises weighing scale 5% to 20%, and 5% aqueous solution of the ethanol that solvent comprises weighing scale 73% to 93% in water.In this embodiment, described compositions plays the effect of the thick gel that does not need to exert pressure for realizing hemostasis fast.Said composition can be delivered locally to damaged blood vessels.
In another embodiment of the invention, the polypeptide that is rich in lysine of the sodium alginate that structural polymer (226) comprises weighing scale 0.1% to 4% and weighing scale 1% to 5%, the diethyllaminoethyl glucosan (DEAE-glucosan) that parent's blood polymer (224) comprises weighing scale 5% to 25%, and 5% aqueous solution of the ethanol that described solvent comprises weighing scale 65% to 93% in water.The aerosol of the pentyl acetate of the nitrocellulose of the calcium chloride that biocompatible polymer composites (114) comprises weighing scale 0.1% to 1% by application afterwards, weighing scale 1% to 5% and weighing scale 94% to 98.9% comes in-situ cross-linked.In this embodiment, said composition plays for hurting with abrasive lasting also restriction from the effect of the protective cover of the water loss of wound.
5% aqueous solution of the ethanol of the sodium alginate that in one embodiment of the invention, biocompatible polymer composition comprises weighing scale approximately 3.6%, the Sea Cure CL 313 of weighing scale approximately 7% and weighing scale approximately 89.4% in water.This embodiment can play the effect of the compositions for the treatment of arterial hemorrhage.
In one embodiment of the invention, the bivalence that described protective finish comprises weighing scale approximately 0.1% to approximately 30% or the more cation of high price; The hydrophobic polymer of weighing scale 0% to approximately 90%; Solvent with weighing scale approximately 5% to approximately 99.9%.In one embodiment of the invention, the bivalent cation that described protective finish comprises weighing scale approximately 0.1% to approximately 1%; The hydrophobic polymer of weighing scale approximately 1 to approximately 5%; And the solvent of weighing scale approximately 94% to approximately 98.9%.
In one embodiment of the invention, compositions (114) is used as for example carrier of medicine or biomolecule of therapeutic agent.Use compositions (114) as drug delivery system, to improve the effect of wound healing gel.In one aspect, silver-colored salt preparation for protective coating (110), the antibacterial characteristics of increase gel.In one embodiment, described therapeutic agent choosing is the group of following composition freely: antimicrobial, antibiotic, hormone, albumen (for example calprotectin, thrombin, thrombinogen, blood coagulation factor VIII) and iodine, and combine.In one embodiment of the invention, described therapeutic agent iodine preferably.In another embodiment of the invention, described therapeutic agent is albumen.
In one embodiment of the invention, crosslinkable polyanion polymer can be poly styrene sulfonate (for example kayexalate), polyacrylate (for example sodium polyacrylate), poly-methyl acrylate (for example sodium polymethacrylate), polyvinyl sulfate (for example polyvinyl sodium sulfate), Quadrafos (for example polyphosphate sodium), ι carrageenan, kappa carrageen glue, gellan gum, carboxymethyl cellulose, carboxymethyl agarose, Sensor Chip CM 5, carboxymethyl chitosan, carboxymethyl chitosan, the polymer of carboxyl methyl group modification, alginate (for example sodium alginate), the polymer that contains a plurality of carboxylate groups, xanthan gum, and combination.Preferably, described crosslinkable polyanion polymer is alginate, more preferably sodium alginate.
Preferably, the biocompatible polymer composition that crosslinkable polyanion polymer comprises weighing scale approximately 1% to approximately 95%; Preferably, the biocompatible polymer composition that crosslinkable polyanion polymer comprises weighing scale approximately 5% to approximately 40%; Preferably, the biocompatible polymer composition that crosslinkable polyanion polymer comprises weighing scale approximately 10% to approximately 30%.
In one embodiment of the invention, not crosslinkable polyanion polymer can be hyaluronate (for example hyaluronate sodium), polynucleotide (for example RNA), have polypeptide chain, glucosaminoglycan and the proteoglycan of the average residue isoelectric point, IP below 7, and combine.Preferably, described not crosslinkable polyanion polymer is hyaluronate, preferred hyaluronate sodium.
Preferably, the biocompatible polymer composition that described not crosslinkable polyanion polymer comprises weighing scale approximately 0 to approximately 95%; Preferably, the biocompatible polymer composition that described not crosslinkable polyanion polymer comprises weighing scale approximately 5 to approximately 25%; Preferably, the biocompatible polymer composition that described not crosslinkable polyanion polymer comprises weighing scale approximately 0 to approximately 5%; Preferably, the biocompatible polymer composition that described not crosslinkable polyanion polymer comprises weighing scale approximately 0 to approximately 2%; Preferably, the biocompatible polymer composition that described not crosslinkable polyanion polymer comprises weighing scale approximately 1 to approximately 5%.
In one embodiment of the invention, polycation polymer can be chitosan (for example Sea Cure CL 313), chitin, diethylamino ethyl-glucosan, DEAE-cellulose, diethylamino ethyl-agarose, diethylamino ethyl-alginate, polymer, the polymer that contains a plurality of protonated amino groups with diethylamino ethyl, modified and the polypeptide with more than 7 average residue isoelectric point, IPs, and combination.Polycation polymer is chitosan preferably, more preferably Sea Cure CL 313.Preferred polycation polymer is diethylamino ethyl glucosan (DEAE-glucosan).
Preferably, the biocompatible polymer composition that polycation polymer comprises weighing scale approximately 1% to approximately 90%; Preferably, the biocompatible polymer composition that polycation polymer comprises weighing scale approximately 2% to approximately 80%; Preferably, the biocompatible polymer composition that polycation polymer comprises weighing scale approximately 2% to approximately 25%.
Each component of biocompatible polymer composition can be stored in various container, is applicable to various application, comprises for example bag, pouch, pipe, bucket, pump, syringe, bottle, bag and aerosol-type aerosol can.Described component can be stored in the container of being made by various materials, for example comprises in plastics, metal or glass.Described component can be operably connected and construct or provide so that user arranges before use as independent component.
Compositions described herein and system can be included in the test kit or goods that is used to form biocompatible polymer composition, and it comprises one or more in following: the solution that comprises polyanion polymer; The solution that comprises polycation polymer; Solvent; With comprise bivalence or the solution of high-valence cationic, hydrophobic polymer and solvent more.In test kit or goods, can also contain gauze, binder, adhesive tape, brush, shovel and sponge.
Some application have been described.Yet, should be understood that the spirit and scope that can carry out various modifications and not depart from presents.Particularly, for example, the various compositions of solution have been described, but similar parts that change and element can be integrated or substitute and utilize to realize same or similar effect.And, can be for different wound sites, the inside of skin or outside skin corium, comprise organ transplantation, any site that tissue transplantation and/or health are outside and/or inner or various surgical incisions and the infringement of position, adopt different substrate.Therefore, within other is applied in the scope of following claim.
Further, the research of description can utilize an embodiment of compositions to form rigid matrix and can, by another compositions, alone or in combination, be designed to have the elasticity of increase simultaneously.Further, the method for mixing and compositions formulated can be carried out with any order and combination, thereby realizes the same or analogous effect of the solidification matrix of embedding, and described substrate is integrated the formation of nature recombinant tissue.In one embodiment, first described one or more polyanion polymer is applied to wound, and afterwards one or more polycation polymer applications on one or more the poly polymer in wound location.In one embodiment, described one or more polyanion polymer and described one or more polycation polymer mixed, is then applied to wound by this mixture.In one embodiment, described one or more polyanion polymer and described one or more polycation polymer applications simultaneously approximately in wound simultaneously or be applied to wound.
In one embodiment, the method for the treatment of wound comprises one or more polyanion polymer applications in wound, and afterwards by one or more polycation polymer applications in described one or more many polymer, polymers of wound location.In one embodiment, the method for the treatment of wound comprises the polymer of one or more polyanion and one or more polycation polymer mixed, and afterwards described mixture is applied to wound.In one embodiment, the method for the treatment of wound is included in one or more polycation polymer applications in the wound time or about identical time, by one or more polyanion polymer applications in wound.
Claims (21)
1. a biocompatible polymer composition, comprises:
A. one or more polyanion polymer of weighing scale approximately 0.1% to approximately 95%;
B. one or more polycation polymer of weighing scale approximately 0.1% to approximately 90%; With
C. the water of weighing scale 0.1% to 99.8%.
2. biocompatible polymer composition as claimed in claim 1, wherein said one or more polyanion polymer comprises at least one crosslinkable polyanion polymer.
3. biocompatible polymer composition as claimed in claim 2, wherein said one or more polyanion polymer also comprises at least one not crosslinkable polyanion polymer.
4. biocompatible polymer composition as claimed in claim 3, the wherein free group of following composition of at least one crosslinkable polyanion polymer choosing: poly styrene sulfonate, polyacrylate, poly-methyl acrylate, polyvinyl sulfate, Quadrafos, ι carrageenan, kappa carrageen glue, gellan gum, carboxymethyl cellulose, carboxymethyl agarose, Sensor Chip CM 5, carboxymethyl chitosan, carboxymethyl chitosan, polymer, the alginate of carboxyl methyl group modification, the polymer that contains a plurality of carboxylate groups and xanthan gum.
5. biocompatible polymer composition as claimed in claim 4, the wherein free group of following composition of one or more crosslinkable polyanion polymer choosing: kayexalate, sodium polyacrylate, sodium polymethacrylate, polyvinyl sodium sulfate, polyphosphate sodium and sodium alginate.
6. biocompatible polymer composition as claimed in claim 3, the free group of following composition of at least one not crosslinkable polyanion polymer choosing wherein: hyaluronate, polynucleotide, there is polypeptide chain, glucosaminoglycan and the proteoglycan of the average residue isoelectric point, IP below 7.
7. biocompatible polymer composition as claimed in claim 6, the wherein free group of following composition of at least one not crosslinkable polyanion polymer choosing: hyaluronate sodium or RNA.
8. biocompatible polymer composition as claimed in claim 3, wherein said one or more the free group of following composition of polycation polymer choosing: chitosan, chitin, diethylamino ethyl-glucosan, DEAE-cellulose, diethylamino ethyl-agarose, diethylamino ethyl-alginate, with polymer, the polymer that contains a plurality of protonated amino groups of the modification of diethylamino ethyl with there is the polypeptide of more than 7 average residue isoelectric point, IPs.
9. biocompatible polymer composition as claimed in claim 3, wherein at least one crosslinkable polyanion polymer is by hydrogen bond and at least one polycation crosslinked polymer.
10. biocompatible polymer composition as claimed in claim 3, wherein at least one crosslinkable polyanion polymer is by covalent bond and at least one polycation crosslinked polymer.
11. biocompatible polymer composition as claimed in claim 3, it also comprises the freely therapeutic agent of the group of following composition of choosing: antimicrobial, antibiotic, hormone, albumen and iodine.
The method of 12. 1 kinds of original position formation protective coatings on polymer composition as claimed in claim 1, comprises adding comprising following solution:
A. the bivalence of weighing scale approximately 0.1% to approximately 30% or more high-valence cationic;
B. the hydrophobic polymer of weighing scale 0% to approximately 90%; With
C. the solvent of weighing scale approximately 5% to 99.9%.
13. methods as claimed in claim 12, wherein said hydrophobic polymer choosing is the group of following composition freely: polyurethanes, nitrocellulose, cyanoacrylate, styrene, politef and silicone.
14. methods as claimed in claim 12, wherein said solvent choosing is the group of following composition freely: water, pentyl acetate, acetone, methyl ethyl ketone, isopropyl alcohol and oxolane.
15. methods as claimed in claim 12, wherein said bivalence or more high-valence cationic choosing be the group of following salt composition freely: Ca
2+, Fe
2+, Fe
3+, Ag
2+, Ag
3+, Au
2+, Au
3+, Mg
2+, Cu
2+, Cu
3+and Zn
2+.
16. 1 kinds of methods of processing wound, comprise directly to wound application biocompatible polymer composition as claimed in claim 1.
17. methods as claimed in claim 16, wherein said wound choosing is the group of following composition freely: outside lacerated wound, wearing and tearing, burn, eye lacerated wound, organa parenchymatosum's damage, inner lacerated wound, gastrointestinal tract lacerated wound, shallow table incised wound and scratch, internal hemorrhage, arterial hemorrhage, venous hemorrhage, tooth or oral hemorrhage and otch.
Realize quick-acting haemostatic powder and without the method for exerting pressure to wound for 18. 1 kinds, comprise directly to wound application biocompatible polymer composition as claimed in claim 1.
19. 1 kinds of biocompatible polymer compositions, comprise:
A. the sodium alginate of weighing scale approximately 1% to approximately 20%;
B. the hyaluronate sodium of weighing scale approximately 1% to approximately 5%;
C. the Sea Cure CL 313 of weighing scale approximately 2% to approximately 20%; With
D. weighing scale 55% to 96% 5% aqueous solution of ethanol in water.
The method of 20. 1 kinds of original position formation protective coatings on polymer composition as claimed in claim 19, comprises adding comprising following solution:
A. the calcium chloride of weighing scale approximately 0.1% to approximately 1%;
B. the nitrocellulose of weighing scale approximately 1% to approximately 5%; With
C. weighing scale approximately 94% to approximately 98.9% pentyl acetate.
21. biocompatible polymer compositions as claimed in claim 1, wherein said solvent choosing is the group of following composition freely: water, ethanol, pentyl acetate, acetone, methyl ethyl ketone, isopropyl alcohol and oxolane.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107708750A (en) * | 2015-06-22 | 2018-02-16 | 克里斯伦公司 | Highly effective hemostasis adhesive polymer support |
| CN115463248A (en) * | 2015-06-22 | 2022-12-13 | 克里斯伦公司 | Highly effective hemostatic adherent polymeric stents |
| CN105030815A (en) * | 2015-08-10 | 2015-11-11 | 贵州扬生医用器材有限公司 | Operation flushing fluid and preparation method of operation flushing fluid |
| CN105030815B (en) * | 2015-08-10 | 2019-03-15 | 贵州扬生医用器材有限公司 | A kind of surgical flush fluid and its preparation method |
| CN105860107A (en) * | 2016-04-26 | 2016-08-17 | 中南大学 | Preparation method of hydrogen-peroxide-responsive chitosan hydrogel with electrochemical activity |
| CN105860107B (en) * | 2016-04-26 | 2018-02-09 | 中南大学 | A kind of hydrogen peroxide response and the preparation method of the aquagel with electro-chemical activity |
| CN110121350A (en) * | 2016-12-22 | 2019-08-13 | 奥姆里克斯生物药品有限公司 | Hemostatic composition comprising anionite and calcium salt |
| CN108926490A (en) * | 2017-05-25 | 2018-12-04 | 南方医科大学南方医院 | A kind of production method of anticoagulant stomach tube |
| CN108926490B (en) * | 2017-05-25 | 2021-01-26 | 南方医科大学南方医院 | Manufacturing method of anticoagulation stomach tube |
| CN111303453A (en) * | 2020-03-09 | 2020-06-19 | 中国海洋大学 | Preparation method and application of multiple sensitive hydrogel polymer |
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